Rehydratable product and method of preparation thereof

ABSTRACT

A hydratable iontophoretic bioelectrode includes a plurality of layers of material capable of absorbing and holding an ionized fluid when placed in contact with the fluid. Adjacent layers are maintained at least partially out of contact from one another by disposition between the layers of spacing elements such as sugar or other dissolvable particles or cellulose. The edges of the layers may be crimped to maintain the layers in a stack for assembly with an electrode sheet; such a sheet would be provided for receiving an electrical current to thereby produce an electric field and cause a migration of ions of the ionized fluid away from the electrode sheet and into the skin or tissue of a person or animal against which the bioelectrode is placed.

This is a continuation-in-part application of application Ser. No.383,939, filed Jul. 21, 1989, now U.S. Pat. No. 5,087,242.

BACKGROUND OF THE INVENTION

This invention relates to a rehydratable product or membrane especiallysuitable for use in an iontophoretic bioelectrode system, and to amethod of preparing the rehydratable membrane.

Iontophoretic bioelectrodes, used in place of hypodermic needles toinject medications into a person's skin or tissue, typically include apouch or similar enclosure formed with a wettable barrier or amicroporous membrane on one side thereof. See, for example, U.S. Pat.Nos. 4,250,878, 4,419,092 and 4,477,971. A medication solutioncontaining ions to be delivered into the person's skin or tissue isinjected into the pouch by means of a hypodermic needle, syringe, etc.When the wettable barrier or membrane is placed against a person's skinand an electric current is supplied to the solution, the ions are causedto migrate from the solution through the wettable barrier or membrane,and into the skin.

A second bioelectrode is used in conjunction with the above-describediontophoretic bioelectrode, but does not include a solution of ions.Rather, the second bioelectrode need only include an element for makingcontact with the person's skin or tissue (generally in close proximityto the iontophoretic bioelectrode), such as a wettable barrier ormembrane for allowing migration of current (of opposite polarity to thatof the current supplied to the iontophoretic bioelectrode) between theperson's skin or tissue through the contact element to a second currentsource.

For the iontophoretic bioelectrode described earlier, barriers ormembranes are required to retain the solution in the pouch whileallowing ions to migrate therethrough. However, such barriers ormembranes also inhibit wetting of the skin and thus inhibit themigration of ions to a certain extent, at least as compared to asituation where the solution were in direct contact with the skin. Also,because of the use of a pouch or similar enclosure to contain themedication solution, a mechanism or structure on the enclosure isnecessary for allowing the injection thereinto of the solution. Suchstructure has typically included some type of orifice containing a pluginto which a hypodermic needle or syringe tube may be inserted to allowdelivery of the solution through the orifice into the interior of theenclosure, while preventing the outflow of the solution after it hasbeen injected into the enclosure. The requirement of such solutionreceiving mechanism or enclosure, of course, increases the cost of thebioelectrode and gives rise to potential leakage locations.

In copending patent application, Ser. No. 383,939, a hydratablebioelectrode is disclosed in which the need for special solutionreceiving structure or mechanisms is obviated. This bioelectrodeincludes a layer of material for absorbing and holding aqueous solutionswhen placed in contact therewith, a conductive sheet disposed in closeproximity to the layer of material for receiving an electrical charge tothereby cause ions in the fluid to move to and from the layer ofmaterial toward or away from the conductive sheet, and a support base onwhich the layer of material and conductive sheet are mounted. The layerof material may comprise a polymer, a matrix of fibers impregnated orinterwoven with a hydratable polymer, or similar ion solution absorbingmaterial. This bioelectrode structure provides a simple, inexpensive andeasy to use iontophoretic delivery mechanism.

SUMMARY OF THE INVENTION

It is an object of the invention to provide a method and structure for asimple, inexpensive, and skin contour conformable iontophoreticbioelectrode.

It is also an object of the invention to provide such an iontophoreticbioelectrode capable of efficiently absorbing and holding an aqueoussolution when placed in contact therewith.

It is an additional object of the invention to provide such aniontophoretic bioelectrode which may be constructed using conventionalequipment.

The above and other objects of the invention are realized in a specificillustrative embodiment of a hydratable bioelectrode for deliveringmedicament into the skin or tissue of a person or animal, where themedicament is ionized. The bioelectrode includes a hydratable element104 for absorbing ionized medicament in aqueous solution when placed incontact therewith, apparatus for holding the hydratable element, and anelectrode mounted on the holding apparatus in proximity to thehydratable element for receiving an electrical current to therebyproduce an electrical field and cause ionized medicament to move fromthe hydratable element into the skin or tissue on which the bioelectrodeis placed. The hydratable element, in turn, includes a stack of at leasttwo sheets of hydrogel for absorbing medicament, separating elements formaintaining adjacent sheets at least partially separated, and structurefor holding the sheets in the stack. An alternative to use of separatingelements would be to form fluid channels between the sheets.

In accordance with one aspect of the invention, the separation elementsare comprised of granules or fibers disposed between each pair ofadjacent sheets of hydrogel, with such granules or fibers comprising,for example, sugar crystals, cellulose fibers, etc.

In accordance with another aspect of the invention, the sheets ofhydrogel are formed to be relatively stiff to enable maintaining thesheets apart from one another by the separation elements so that whenthe sheets are exposed to medicament for absorbtion thereof, there is agreater surface area of the hydrogel sheets in contact with themedicament and thus there is a more rapid complete and uniformabsorbtion.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other objects, features and advantages of the inventionwill become apparent from a consideration of the following detaileddescription presented in connection with the accompanying drawings inwhich:

FIG. 1A and 1B show a flow diagram of a method of constructinghydratable bioelectrodes in accordance with the principles of thepresent invention;

FIG. 2 shows a side, cross-sectional view of a starting product for usein the method illustrated in FIG. 1; and

FIG. 3 is an end, cross-sectional view of an iontophoretic bioelectrodemade in accordance with the principles of the present invention.

DETAILED DESCRIPTION

FIG. 1 is a flow chart showing the steps of one embodiment of a methodof producing a hydratable bioelectrode in accordance with the presentinvention. An exemplary starting material for the method of FIG. 1 isshown in cross section in FIG. 2 to include a mass of gel material 204sandwiched between two layers of liner material 208 and 212 made, forexample, of plastic. A sheet of scrim (mesh material) 216 is disposed inthe gel mass generally midway between the two liners 208 and 212. Thestarting material illustrated in FIG. 2 might illustratively be an inerthydrogel identified as STD-1 or WD-1 which are the products of Nepera,Inc. used as a skin dressing for wounds, burns, etc. These particularhydrogels constitute a polyethylene oxide polymer which is crosslinked,for example, using e-beam radiation, by chemical means, or by otherstrong radiation such as gamma rays. The starting material could also bea polyacrylamide polymer, copolymer, or other polymer capable ofabsorbing water.

Referring now to FIG. 1, the first step of the method or process ofproducing a hydratable bioelectrode is to provide a starting materialsuch as that shown in FIG. 2. From such a stock piece of material, astrip of, for example, six inches by thirteen inches is cut out in aconventional fashion (step 108 of FIG. 1) and then laid flat on a tableto allow peeling off of the top liner sheet 208 (steps 112, 116 and 120of FIG. 1). (The term "PEO" used in some of the steps of FIG. 1 means"polyethylene oxide", and the term "WIP" means "work in process".)Although the steps shown in boxes 112, 116 and 120 of FIG. 1 are ratherspecific for peeling off the top liner 208 of the starting material ofFIG. 2, it should be understood that any of a variety of approachescould be taken for removing the liner; further starting material withoutany liner to begin with could be provided and then, of course, steps112, 116 and 120 would not be necessary.

After step 120 of FIG. the gel mass or layer 204 and remaining liner 212are wound about a roller device so that the gel layer 204 facesoutwardly. The next step in the process is to place afluoroplastic-coated tray onto a cold table to cool the tray, with thetray being held in place by a vacuum in a conventional fashion. When thetray reaches a steady state temperature of, for example, eighteendegrees Fahrenheit (a temperature below the freezing point of the gellayer), as indicated in step 124, the roller, with gel layer woundthereabout, is aligned along one edge of the cooled tray (step 128) androlled at a predetermined, controlled rate to cause the outward facingor upper layer of the gel material 204 to freeze and hold onto the trayso that as the roller continues to roll, the thin upper layer (down tothe scrim 216) is peeled away from the remainder of the gel on theroller and frozen onto the tray. If no scrim 216 were present in the gelmass 204, the tray temperature, and rate of rolling the roller, woulddetermine the thickness of the layer of gel which is frozen to the trayand peeled from the roller. A layer of gel is now disposed on the trayand another gel layer sandwiched between the scrim 216 and liner 212remains on the roller.

With the layer of gel on the tray, after step 132 the tray is placed ina convection drying chamber (step 136) which has been heated to about55° centigrade. The purpose of this is to dry the gel layer at atemperature which will not cause degradation of the gel (typically about60° centigrade). The dried gel layer is then removed according to step140 from the tray and placed onto a screen and clamped to maintain theplanarity of the layer (steps 144 and 148), and the screen is thenimmersed in a "swelling" solution of water (step 152) containing astiffening agent such as sugar, for example, 50 grams per liter. Thepurpose of the stiffening agent will be discussed later. The screen onwhich the gel layer is placed may illustratively be a perforatedfluoro-coated metal sheet, with another screen on top to maintain theflatness of the gel layer.

The screen with gel layer remains submerged in the swelling solution fora sufficient time to allow the layer to absorb solution, swell andexpand laterally (step 156). The screen with swollen gel layer is thenremoved from the swelling solution, blotted dry (step 160) and aftersufficient blotting, the screen with gel layer is again placed in theconvection drying chamber to further dry the gel layer (step 164 andstep 168). After swelling and the final step of drying, the gel layerwill have substantially the same length and width dimensions, but thethickness will have decreased substantially from when wet.

In the next stage of the process, granules or fibers are distributedonto the gel layer to serve as spacers to maintain apart, to the extentpossible, adjacent gel layers which will later be used to form a stackof gel layers. Individual gel layers will be fairly stiff, as a resultof immersion thereof in the swelling solution with stiffening agent, andso the distribution of granules or fibers, such as sugar or saltcrystals or cellulose, over the gel layers will serve as spacers whenthe gel layers are placed in a stack. One way of distributing thegranules or fibers onto the gel layer is to place the gel layer onto aconveyor belt and pass it under a granule/fiber dispenser (step 172 andstep 176). It is desired to maintain individual gel layers separatedwhen in a stack so that when hydrated with iontophoretic medicament, themedicament will be allowed to flow between the layers and thus be morerapidly and uniformly absorbed by the ultimate gel layer stack.

In step 180 and 182, a fine water vapor or mist is applied to the gellayer simply to better hold the granules or fibers on the gel layersurface. The water vapor or mist partially dissolves granules such assugar causing them to "stick" onto the gel layer. It is important thattoo much water vapor or mist not be used so that the granules are notdissolved completely, since, of course, they would then not serve tomaintain the gel layer separated from adjacent layers.

After securing the granules or fibers onto the gel layer, the gel layeris removed from the screen (step 184) and then arranged in a stack withother gel layers, for a total, for example, of 28 layers (step 186). Asufficient number of gel layers are included in a stack so that when thegel layers are incorporated into a bioelectrode such as that shown inFIG. 3, the electrode sheet 304 which receives electrical current from acurrent source 308 will not burn the skin or tissue of a person againstwhich the bioelectrode is placed. On the other hand, if too many layersare used to form the stack, then assembly may become too costly.

After the layers are formed into a stack, the stack is presscut by aroller press (step 188) which both cuts the stack lengthwise, forexample, and also crimps the resulting adjacent edges so cut. FIG. 3shows opposite edges 312 and 316 of a gel layer stack which have beencrimped and cut. Note that the edges which are crimped are much thinnerthan the center portion of the stack which, of course, has not beencrimped. In step 190 and 192, the stack is then cut perpendicularly tothe press-cut made in step 188 to thereby provide a plurality ofindividual stacks of gel layers, each of which may then be incorporatedinto a bioelectrode structure such as that shown in FIG. 3 (step 194 ofFIG. 1).

In the manner described, a simple iontophoretic bioelectrode is providedin which the ionized medicament may be absorbed into a stack of gellayers which are part of the bioelectrode. The hydratable layers maythen be placed in direct contact with the skin or tissue of a person oranimal for administering the medicament and because the gel layers arein direct contact, improved wetting of the skin or tissue, and thus moreefficient delivery of the ions, is achieved.

It is to be understood that the above-described arrangements are onlyillustrative of the application of the principles of the presentinvention. Numerous modifications and alternative arrangements may bedevised by those skilled in the art without departing from the spiritand scope of the present invention and the appended claims are intendedto cover such modifications and arrangements

What is claimed is:
 1. A bioelectrode for iontophoretically deliveringmedicament into the skin or tissue of a person or animal comprising:ahydratable element for absorbing ionized medicament when placed incontact therewith, means for holding the hydratable element, anelectrode mounted on the holding means in proximity to the hydratableelement for receiving an electrical current to produce an electricalfield and cause ionized medicament to move from the hydratable elementinto the skin or tissue on which the bioelectrode is placed, whereinsaid hydratable element comprises a stack of at least two horizontallypositioned sheets of hydrogel for absorbing medicament interspaced withgranules or fibers as means for maintaining adjacent sheets at leastpartially separated, and means for holding the sheets in the stack.
 2. Abioelectrode as in claim 1 wherein said sheets of hydrogel are formed tobe relatively stiff.
 3. A bioelectrode as in claim 2 wherein saidhydrogel sheets comprise a composition of a polymer and sugar.
 4. Abioelectrode as in claim 1 wherein said separating means are granules.5. A bioelectrode as in claim 4 wherein said granules comprise sugarcrystals.
 6. A bioelectrode as in claim 1 wherein said separating meanscomprises granules or fibers spaced apart to form channel forming meansdisposed between each pair of adjacent sheets of hydrogel for allowingthe flow of medicament therebetween.
 7. A bioelectrode as in claim 1wherein said hydrotable element holding means comprises crimpingtogether of corresponding edges on opposite sides of the sheets ofhydrogel.
 8. A bioelectrode as in claim 1 wherein said hydrogel sheetsare comprised of cross-linked polymer.
 9. A bioelectrode as in claim 8wherein said polymer is polyethylene oxide.
 10. A bioelectrode as inclaim 8 wherein said polymer is polyacrylamide.
 11. A rehydratableproduct for use in a bioelectrode wherein said rehydratable productcontacts the skin or tissue of a person or animal on whom thebioelectrode is placed, comprising:a plurality of horizontallypositioned sheets of hydrogel disposed together in a stack for absorbinga medication solution interspaced with granules or fibers as means forat least partially spacing apart adjacent sheets of hydrogel; and meansfor holding the sheets of hydrogel together in the stack; and whereinsaid sheets of hydrogel are formed with a stiffening agent.
 12. Aproduct as in claim 11 wherein said stiffening agent is sugar.
 13. Aproduct as in claim 11 wherein said spacing means comprises granules orfiber spaced apart to form channels for carrying solution into contactwith the sheets of hydrogel.
 14. A product as in claim 11 wherein saidspacing means are sugar granules.
 15. A product as claim 11 wherein saidgranules are sugar crystals.
 16. A product as in claim 12 wherein saidgranules are cellulose particles.